The specific objectives of our research are to (a) define the mode of action and structure-activity relationships for certain antitumor and antiviral agents, (b) select, on structural grounds, organic compounds that inhibit attachment of viral mRNA to ribosomes, (c) determine mechanisms of resistance to antiviral drugs, and (d) study the molecular basis for the interaction of certain antitumor agents with macromolecules. Among the agents that will be studied are: (a) inhibitors of macromolecular synthesis (anthramycin, camptothecin and ricin), (b) inhibitors of attachment of mRNA to ribosomes (aurintricarboxylic acid and related triphenylmethane dyes), and (c) established antiviral agents (gliotoxin, hydroxybenzylbenzimidazole and camptothecin). In addition, the interaction of some of these compounds with their presumptive cell receptor (e.g., anthramycin with DNA) will be studied by high resolution nuclear magnetic resonance and other biophysical techniques. Determining the mode of action of such compounds is of value in establishing normal pathways of macromolecular synthesis as well as in correlating biochemical function with therapeutic activity. Furthermore, knowledge of the mode of action can suggest new uses for a particular drug and may warn against unsuspected toxicities. Using biochemical information gained from some of our studies, we will attempt to design new therapeutic agents with potential antiviral activity.